Infants are at increased risk for serious complications from influenza, with morbidity rates exceeding even adults >65 years. Unfortunately, influenza vaccines are ineffective in infants <6 months of age. This biologically vulnerable group relies on maternal antibody for protection. Public health officials advocate maternal immunization; however, there is no data on which type of maternal influenza vaccine best protects infants. We seek to compare maternal response to the systemic inactivated influenza vaccine (TIV) and the intranasal live-attenuated influenza vaccine (LAIV). Because the lactating mammary gland is part of mucosa-associated lymphoid tissue, we hypothesize that mucosally-administered LAIV will elicit higher levels of anti-influenza immunity in breast milk than vaccination with the injeced TIV. We will evaluate levels of influenza-specific antibodies and cellular immunity in blood and breast milk. We also will compare levels of influenza-specific responses in TIV and LAIV recipients. Finally, we will perform gene expression experiments to identify gene expression patterns induced after vaccination to further understand differences in innate and adaptive immune responses. Our data will provide a comprehensive analysis of the mechanisms underlying immune protection during breastfeeding. Moreover, the experience and knowledge gained from this proposal will lay the foundation for an R01 application for support for further investigations of how to optimize this maternal vaccination strategy for the protection of infants against influenza and other infectious diseases.